| First Author | Wang S | Year | 1992 |
| Journal | Am J Hum Genet | Volume | 51 |
| Issue | 4 | Pages | A204 (Abstr.) |
| Mgi Jnum | J:2915 | Mgi Id | MGI:51433 |
| Citation | Wang S, et al. (1992) HMG CoA Lyase (HL): Characterization of a mouse liver cDNA and chromosomal mapping in human and mouse. Am J Hum Genet 51(4):A204 (Abstr.) |
| abstractText | Full text of Abstract: 3-hydroxy-3-methylglutaryl Coenzyme A Lyase (HL) is a mitochondrial matrix enzyme which catalyses the last step of ketogenesis. The autosomal recessive deficiency of HL causes hypoglycemia and coma. We have cloned a human HL cDNA (HLH1) (Mitchell et al., Am. J. Hum. Genet. 1991, 49:101). Using HLH1 as a probe we isolated a 1.4 kb fragment (HLM) from a mouse liver cDNA library in lambdagt11. The sequence was extended in the 5' nontranslated region using rapid amplification of cDNA ends (RACE) PCR to include the initiation methionine codon and part of predicted mitochondrial leader. We sequenced the complete murine HL coding and the 3' nontranslated regions. The nucleotide sequence of the coding region of HLM is 85.7% identical to human HL, 73.8% to chicken HL and 52.6% to Ps mevalonii HL. Peptide identities of 87.4%, 80.3% and 54.3%, were observed respectively. Northern analysis showed HL expression in liver, muscle, brain, kidney and ES cells. Southern analysis of 29 inbred mouse strains and M. spretus revealed a total of ~25 kb of hybridizing fragments. The presence of 3 polymorphic fragments allowed us to distinguish between HL from C57BL/6J and M. spretus (SPRET/Ei) in both Eco RI and Hind III digestions. Using a polymorphic Eco RI fragment we analyzed a panel of genomic DNAs from the progeny of a backcross of SPRET/Ei males and F1 females from an interspecific mating (C57BL/6J X SPRET/Ei). Segregation patterns were compared for the mouse HL locus (Hmgcl) and other loci previously typed with this panel. The gene order, Pmv-19 -12.2 +/- 3.4 cM - Hmgcl - 3.3 +/- 1.9 cM - Xmv-8, was established by maximum likelihood analysis (Bishop, 1985, Genet. Epidemiol. 2:349-361), assigning Hmgcl to mouse chromosome 4. Using as a marker amplification of a genomic HL fragment spanning to HLH residues 967 to 1537, HL was localized to human chromosome 1, using a human-hamster hybrid cell panel. Because of the position of Hmgcl on mouse chromosome 4, we predicted that the human HMGCL locus would map to distal 1p. With in situ hybridization using HLH1 as a probe, we analysed the distribution of 300 silver grains and found 19% to be clustered in chromosome 1p35-36.1. |
